Grow fresh cartilage from adult stem cells

U. PENNSYLVANIA (US) — Bioengineers are a step closer to growing new cartilage from a patient’s own stem cells.

Cartilage injuries are difficult to repair. Current surgical options generally involve taking a piece from another part of the injured joint and patching over the damaged area, but this approach involves damaging healthy cartilage, and a person’s cartilage may still deteriorate with age.

“The broad picture is trying to develop new therapies to replace cartilage tissue, starting with focal defects—things like sports injuries—and then hopefully moving toward surface replacement for cartilage degradation that comes with aging,” says Jason Burdick, associate professor of bioengineering at the University of Pennsylvania. “Here, we’re trying to figure out the right environment for adult stem cells to produce the best cartilage.”

“As we age, the health and vitality of cartilage cells declines,” says Robert Mauck, associate professor of orthopedic surgery, “so the efficacy of any repair with adult chondrocytes is actually quite low. Stem cells, which retain this vital capacity, are therefore ideal.”

Burdick and colleagues have long studied mesenchymal stem cells, a kind of adult stem cell found in bone marrow that is capable of turning into bone, fat or cartilage cells. His group has been particularly interested in deducing the microenvironmental signals that tell these cells which way to differentiate.

A recent paper investigated conditions that can preferentially coax these stem cells into becoming either fat-like or bone-like cells while encapsulated in hydrogels, polymer networks that simulate some of the environmental conditions in which stem cells naturally grow.

As reported in the Proceedings of the National Academy of Sciences, the first step in growing new cartilage is initiating chondrogenesis, or convincing the mesenchymal stem cells to differentiate into chondrocytes, which in turn generate the spongy matrix of collagen and sugars that cushions joints.

One challenge in prompting this differentiation is that, despite the low density of adult chondrocytes in tissues, the actual formation of cartilage begins with cells in close proximity.

“In typical hydrogels used in cartilage tissue engineering,” Burdick says. “We’re spacing cells apart, so they’re losing that initial signal and interaction. That’s when we started thinking about cadherins, which are molecules that these cells use to interact with each other, particularly at the point they first become chondrocytes.”

To simulate that environment, the researchers used a peptide sequence that mimics these cadherin interactions, which they bound to the hydrogels used to encapsulate the mesenchymal stem cells.

“While the direct link between cadherins and chondrogenesis is not completely understood,” Mauck says, “what’s known is that if you enhance these interactions early during tissue formation, you can make more cartilage, and, if you block them, you get very poor cartilage formation. What this gel does is trick the cell into thinking it’s got friends nearby.”

To test the efficacy of their cadherin-mimicking peptide, the researchers encapsulated mesenchymal stem cells in several other kinds of gels: a regular hydrogel with no peptide; one with a non-functional, scrambled version of the peptide; and one with the peptide as well as an antibody that blocked cadherin interactions.

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After a week, cells within gels containing the cadherin peptide exhibited more genetic markers of chondrogenesis than any of the controls.

A second experiment involved growing gels for four weeks, long enough for them to start developing cartilage matrix. This allowed the researchers to conduct functional tests, such as subjecting them to mechanical loads. They found the peptide-containing gels performed more like natural cartilage than the other gels.

The researchers also sectioned the gels and stained them for type-II collagen and chondroitin sulfate, molecules that are part of the cartilage matrix. Once again, the peptide-containing gels produced more of these markers of matrix formation than the controls.

“All together,” Burdick says, “these experiments provide a thorough demonstration that this cadherin signal can improve the chondrogenesis response when presented from a synthetic hydrogel.”

“Moving forward,” adds Mauck, “it will be important to see how these early cell fate decisions translate into longer term tissue function in vivo.”

The research was support by the National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering.

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20 Comments

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Lucy Galea August 17, 2013

Hi my husband Joe is in desperate need of new cartilage in both knees but is reluctant to get knee replacements as he is only 44 years old and a very active person. He is great pain and shouldn’t be working but he keeps pushing himself and I’m afraid of what may happen in the near future. We would be happy to be involved in any trials if you plan any. We are in Australia but are willing to come out and try anything. Do you have any trials happening regards Lucy

RICHARD NORTH August 30, 2013

Due to my scientific background, refusing knee surgery 15 years ago, being knee pain free except steep downhill; I will be a good candidate for knee research.

Ellyn September 15, 2013

I have skeptical yet moderate hopes for growing cartilage from adult stem cells. I’m 25 years old, have Stickler Syndrome Type I, and have had two arthroscopies on and a bone and cartilage transplant on my left knee. My knee still bothers me, so I’ve limited my physical activities and avoid certain professions. I hope it all works out successfully and looking forward to when it can help improve people’s lives.

Kim November 5, 2013

Labrum tears in hips and would like to know how a person becomes a candidate for this adult stem cell research. Tried PRP(platelet rich plasma) injections however insurance doesn’t cover and need to have them on a regular basis to see possibly a difference.

J R Nathan November 16, 2013

My doctor recently advices that my right knee is literally bone on bone and there is no cartilage. With the help of hyaluronic acid tablets and anti-inflammatory tablets I am managing. I am not dependent on anti-inflammatories. I have very good skin constitution to heal no blemishes suggestions that stem cell therapy will work for me. I am 58 years old and have have had osteoarthritis since 2003. What do I need to do to participate in this program.

Travis Minser November 22, 2013

I’ve had my ankle joint replaced, however I still have an area of bone on bone. I’m willing to do any trials or whatever is needed to help in moving forward with your research.

Cartilage earrings jewelry December 17, 2013

Because of my experimental foundation, rejecting knee surgery 28, being knee torment free aside from steep downhill. I think I will be an exceptionally hopeful person for future research.

Cartilage earrings jewelry December 17, 2013

Because of my experimental foundation, rejecting knee surgery 28, being knee torment free aside from steep downhill. I think I will be an exceptionally hopeful person for future research.

way to young to experience osteoarthritis only 53 and have had knee pain and swelling in the left knee particularly but pain in both. doctor is recommending knee replacement – oh no! would like to know about any and all alternatives and study. Any help is appreciated!

Stephen Zulauf February 6, 2014

Keep our hopes alive. Congrats on all your growing knowledge and achievements regarding stem cell for articular cartilage. I’m currently a 39 year old police officer who damaged my knee in the line of duty. I currently have grade 3 and grade 4 damage to my left knee. I’m praying that my knee can one day be revived. Stem cell therapy brings me hope. Hopefully time is on my side. This is one race that I have to win. Please feel free to email me when you need healing volunteers. Thank you. I still wish to protect and serve.

carolyn west February 12, 2014

need ankle replacement would love to find out more.

Dan Reich March 13, 2014

I would like additional information on this issue. I have issues with bone on bone in my right knee. Only in the inside chamber of the knee. The center and outside are not an issue.

Jeff March 18, 2014

I’m a young healthy 44 years old with horrible arthritis in both knees. I do have Stickler syndrome to deal with as well. I would love to participate in this program. Please contact me for more details as my doctor is recommending surgery for my knees.

Margaret March 20, 2014

I was very active and for the past year, I’ve been very limited with activities. I’m 48 years old and I’m constantly on my feet at work. I had right knee sx in the past and since then, I have received cortisone injections and physical therapy that helped but, not any longer. I would like some more information and let me know if I would be a potential candidate for any trials you may be offering.
Thanks,
M

Geoff April 6, 2014

I am 70 with a very painfully right knee which I am told is almost bone to bone and in the uk all I can get is pain killers I would be willing to undergo this treatment
I sail and play golf and wish to carry on as long as I can, I do not want a knee replacement !!!

Joseph McGee May 3, 2014

My x-rays show very little cartilage under the patella and very little on one side laterally on both knees. I am in some pain,trying to lose 20 lbs.I am 61 years old taking only Naproxen Sodium and “Reliv”-“atrhaffect”twice daily. Would stem cell transpant repair my missing or minimal cartilage? Please respond.I am desperate to avoid surgery.–Joseph McGee

C. McCoy May 10, 2014

I have had a problem with flexibility in my shoulders especially in my right shoulder. About a week ago my right shoulder was in a lot of pain more than usual I made an appointment with a Bone and Joint Clinic . They did x-rays on my shoulders and the x-rays shows there were no cartilage in my right shoulder bone on bone, there were some cartilage in my left shoulder. the doctor recommended a shoulder replacement, that I do not want, I am very active in sports please let me know what are some alternatives.

Janet fuentes May 17, 2014

My daughter is 14 years old she had a surgery, she is a dancer and after surgery still having hip pain due to cartilage problems. Please I am desperate to find something that works for this young person.

JAMES ORR December 21, 2014

Just curious, if you could take cells out of an injured knees’ cartilage and grow them in a petri dish, like they do skin cells, and reinstall.